Jay Short: Well, I think, two things. We have both. We have an ADC that just happened to be ready first, and then we also have a biospecific, which I believe we’ve reported on in previous conferences. But I think that there are a couple of reasons why Nectin-4. Number one, there is an associated toxicity with the current marketed Nectin-4 that limits its applicability. Secondly, as we’re going to report on in April at AACR, we’re seeing efficacy in tumors that were not addressable with the current marketed drug. And so we see an opportunity to move, expand indications and also improve on existing indications. And that’s driven, of course, by our novel NextGen carbohydrate linker, which reduces off-target levels of — off-target toxicity that is a result of the payload coming off prior to entering the cancer cell.
And so in general, we see both of these assets have an important opportunity for a validated target. And in general philosophically, I mean, you could ask the same question of CTLA-4. Here’s a drug with incredible opportunity, but the toxicity has been very difficult to manage and has been used in a very limited extent relative to what its potential is. And I think we can make that argument across several different targets when we apply our CAB technology, which improves that selectivity between for the cancer cell and protects the normal cell.
Arthur He: I think thanks for the additional color. So if I may, can I squeeze one more. Just curious, I just quickly noticed the AACR presentation you’re going to be doing at — in April. Could you tell us more on the tetravalent T-Cell engage. I believe the B7-H3 target, what’s the special of these design? I’m just curious.
Jay Short: Well, I think it’s what we refer to as kind of a butterfly design. In other words, we have two arms of the antibody that both combined to the tumor cells. So that’s the tumor cell engager. And then we also have two arms that come off the light chains that combined to CD3 receptor. Now we’ve since at least in terms of the EpCAM drug now that we’re binding to a single CD3 arm at a time, whereas we can still bind to two different antigens on the tumor cell. So but this increases your ability to increases the potency of the drug to have this tetravalent structure even in the case where one arm combined to the ton like in the CD3 arm. Certainly, you’re going to get not only affinity, but also avidity in the tumor targeting portion.
So it’s a very nice design from that perspective. But secondly, because — there’s only one form of this antibody that can be generated during manufacturing. It simplifies manufacturing and reduces cost of goods, which is also an advantage.
Arthur He: Got you. Thanks, Jay. I’ll talk to you soon.
Operator: Thank you. Our next question comes from the line of Ren Benjamin with Citizens JMP. Please proceed with your question.
Reni Benjamin: Hey, good afternoon guys. Thanks for taking the questions. As I think about 3071, I guess, one question is, now you’re looking at the one gram dose level. At what point do you kind of stop dosing higher or can you just continue to go higher until you reach a DLT. And then I guess the second question is, when I’m thinking about the melanoma non-small cell combination with pembro cohorts, for which we’ll have a data readout in the second half of this year. Can you talk, I don’t know, roughly kind of metrics that you might need to meet, like, for example, in melanoma should I be thinking about you guys beating or trying to beat NIVO plus Yervoy from both an efficacy and safety perspective or are you more concerned about the safety aspect and the same kind of question for non-small cell lung cancer.
Jay Short: Eric, do you want to start on this one?
Eric Sievers: Sure. I think I’ll take a start and then hand to Sherry. You had a really interesting question about really how high to go with CTLA-4 inhibition. It’s really striking to look back at earlier randomized trials of ipilimumab 10 per kilo versus 3 per kilo, and the survival benefits are really quite striking at multiple years of follow-up. However, Ipi 10 per kilo was associated with considerable toxicity. So most sponsors that are pursuing CTLA-4 antibody really want to push the dose to achieve high exposures. And then we also want a good, high concentration trough in our pharmacokinetics, so that CTLA-4 blockade lingers of the full three weeks between doses. So our current plan is to treat the patients at one gram every three weeks.
And we don’t plan to go higher. We felt that represents 14.2 milligrams per kilogram, if you compared it to the Ipi dosing. And I think we can use that and just have a broad goal of giving as much CTLA-4 blockade as early in a cancer patient’s treatment as possible and make this something that based on tolerability and its efficacy would be reached for as often as a PD-1 inhibitor. Sheri, do you want to address the questions of regarding what we would see in the context of melanoma and non-small cell lung cancer.
Sheri Lydick: Sure, sure. Thank you, Eric, and thank you, Ren, for your question. I think basically, what we would like is to be meaningfully better than the current marketed standard of care. So what that means is meaningfully better not only in terms of efficacy, but also tolerability. So providing a regimen that will allow a patient who really experience the full benefit of the therapy. So in the context of melanoma whether that means being meaningfully better than Opdualag in terms of efficacy or meaningfully better than Opdivo, Yervoy. We aim to be meaningfully better than what those regimens currently provide.
